Treatment outcomes and resistance patterns of children and adolescents on second-line antiretroviral therapy in Asia

• Main Authors: Wasana Prasitsuebsai, Sirinya Teeraananchai, Thida Singtoroj, Khanh Huu Truong, Jintanat Ananworanich, Viet Chau Do, Lam Van Nguyen, Pope Kosalaraksa, Nia Kurniati, Tavitiya Sudjaritruk, Kulkanya Chokephaibulkit, Stephen J. Kerr, Annette H. Sohn
• Format: Journal
• Published: 2018
• Subjects: Medicine
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84977671951&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/56104
• Institution: Chiang Mai University

© 2016 Wolters Kluwer Health, Inc. Background: Data on pediatric treatment outcomes and drug resistance while on second-line antiretroviral therapy (ART) are needed to guide HIV care in resource-limited countries. Methods: HIV-infected children <18 years who were switched or switching to second-line ART after first-line failure were enrolled from 8 sites in Indonesia, Thailand, and Vietnam. Genotyping was performed at virologic failure (VF; HIV-RNA >1000 copies/mL). Cox proportional hazards regression was used to evaluate factors predicting VF. Results: Of 277 children, 41% were female. At second-line switch, age was 7.5 (5.3-10.3) years, CD4 count was 300 (146-562) cells per cubic millimeter, and percentage was 13 (7-20%); HIV-RNA was 5.0 (4.4-5.5) log 10 copies per milliliter. Second-line regimens contained lamivudine (90%), tenofovir (43%), zidovudine or abacavir (30%), lopinavir (LPV/r; 91%), and atazanavir (ATV; 7%). After 3.3 (1.8-5.3) years on second-line ART, CD4 was 763 (556-1060) cells per cubic millimeter and 26% (20-31%). VF occurred in 73 (27%), with an incidence of 7.25 per 100 person-years (95% confidence interval [CI]: 5.77 to 9.12). Resistance mutations in 50 of 73 children with available genotyping at first VF included M184V (56%), ≥1 thymidine analogue mutation (TAM; 40%), ≥4 TAMs (10%), Q151M (4%), any major LPV mutation (8%), ≥6 LPV mutations (2%), and any major ATV mutation (4%). Associations with VF included age >11 years (hazard ratio [HR] 4.06; 95% CI: 2.15 to 7.66) and HIV-RNA >5.0 log 10 copies per milliliter (HR 2.42; 95% CI: 1.27 to 4.59) at switch and were seen more commonly in children from Vietnam (HR 2.79; 95% CI: 1.55 to 5.02). Conclusions: One-fourth of children developed VF while on second-line ART. However, few developed major mutations to protease inhibitors.